ABSTRACT Fibromyalgia is a chronic widespread pain condition that is most prevalent in middle-aged women. Exercise is one of the few therapies that can alleviate fibromyalgia symptoms. Despite exercise being a major component of rehabilitation, exercise guidelines are unclear, often leading to symptom exacerbation and low compliance. Factors critical to exercise prescription that are not known include: 1) the most effective mode of exercise (e.g., static vs. dynamic contractions); 2) mechanisms responsible for pain relief; and 3) biopsychosocial influences. This study addresses exercise as a nonpharmacological pain management tool for people with fibromyalgia. Our understanding of exercise-induced hypoalgesia is primarily based on studies that include high-intensity exercise performed by young healthy male athletes, which is not applicable to the middle-aged woman with fibromyalgia. We have shown that women with fibromyalgia have considerable variability in pain relief following static exercise. We hypothesize that the attenuated pain relief following exercise is related to abnormal pain modulation involving descending inhibitory pain pathways. Our preliminary data with healthy adults shows that individuals with more efficient pain modulation (i.e., conditioned pain modulation) report greater pain relief with static exercise. Whether this relation observed in healthy adults remains in those with fibromyalgia is not known. This proposal will explore the efficacy of dynamic and static fatiguing contractions in modulating pain relief and the relation to conditioned pain modulation in healthy adults and people with fibromyalgia. First, we will establish if exercise-induced pain relief is dependent on the type of exercise contraction in people with and without fibromyalgia. Experimental and clinical pain reports will be compared before and after the performance of dynamic and intermittent static contractions at submaximal loads performed at the same relative intensity. Second, we will determine whether conditioned pain modulation predicts exercise-induced pain relief. Experimental pain reports will be measured with and without a noxious stimulus (i.e., ice water bath) as a measurement of conditioned pain modulation. We hypothesize: 1) people with fibromyalgia will exhibit attenuated and more variable exercise-induced pain relief compared with people without fibromyalgia; 2) pain relief will be greater following dynamic exercise than static exercise; and 3) conditioned pain modulation will be associated with the magnitude of pain relief following exercise, which will be less in people with fibromyalgia. This project will also investigate several biopsychosocial factors (physical activity levels, pain catastrophizing, and fear avoidance behaviors) that may contribute to pain perception, pain relief with exercise, and conditioned pain modulation. The incorporation of biopsychosocial attributes promotes a person-centered approach to address the heterogeneity in fibromyalgia while identifying profiles of people with fibromyalgia who will benefit most from exercise. Successful completion will establish principles necessary to create clinical practice paradigms for exercise as an effective pain management tool and biopsychosocial influences on this response.